Long-term follow-up of task-specific tremor after thalamotomy: a retrospective observational study.

OBJECTIVE: This study aimed to report the long-term results of thalamotomy in 23 patients with task-specific tremor. METHODS: Data of 23 patients with task-specific tremor who underwent ventralis intermedius nucleus and posterior part of ventro-oral nucleus thalamotomy at the Tokyo Women's Medical University Hospital between 2010 and 2022 were retrospectively analyzed. To evaluate neurological conditions, the severity of task-specific tremor was divided into 0 (no tremor), 1 (slightly tremulous), 2 (moderately tremulous), 3 (accomplishing tasks with great difficulty), and 4 (unable to complete tasks). We also used the subscores "handwriting" (0-4) and "spiral drawing" (0-4) of the Clinical Rating Scales for Tremor. Evaluation scales were presented as medians and interquartile ranges. RESULTS: The severities of task-specific tremor were 3.0 (3.0-4.0) preoperatively and 0.0 (0.0-0.0, p < 0.0001) at the last available evaluation. The writing and spiral drawing of the Clinical Rating Scales for Tremor significantly improved from 3.0 (3.0-4.0) and 3.0 (2.0-3.0) preoperatively, respectively, to 0.0 (0.0-0.0, p < 0.0001) and 0.0 (0.0-0.0, p < 0.0001) at the last available evaluation, respectively. The mean clinical follow-up period was 62.7 ± 26.0 months. Seven (30.4%) patients had focal hand dystonia, which newly developed on the ipsilateral side of the tremor at 2-45 months after the surgery. No serious complications were observed. INTERPRETATION: Thalamotomy significantly improves task-specific tremor with high long-term efficacy, and long-term follow-up is important because focal hand dystonia can develop postoperatively.

Hypertensive cerebral hemorrhage with undetectable plasma vascular endothelial growth factor levels in a patient receiving intravitreal injection of aflibercept for bilateral diabetic macular edema: a case report.

BACKGROUND: Intravitreal injections of anti-vascular endothelial growth factor are commonly used to treat macular diseases, including diabetic macular edema. Anti-vascular endothelial growth factor drugs can enter the systemic circulation after intravitreal injections and appear to suppress circulating vascular endothelial growth factor levels. However, whether this can cause any systemic adverse events remains unknown. CASE PRESENTATION: A 70-year-old Japanese man diagnosed with diabetic macular edema in both eyes was treated with anti-vascular endothelial growth factor intravitreal injections. One month after receiving two intravitreal injections of aflibercept 1 week apart for diabetic macular edema in both eyes, he complained of a severe acute headache. The patient was diagnosed with hypertensive cerebral hemorrhage of the occipital lobe based on an elevated blood pressure of 195/108 mmHg and the results of computed tomography and magnetic resonance imaging of his brain. The patient was treated with an intravenous injection of nicardipine hydrochloride to lower his systemic blood pressure. Two days after the stroke, the patient began oral treatment with 80 mg/day telmisartan, which was continued for 3 days, and the telmisartan dose was reduced to 40 mg/day thereafter. His blood pressure promptly dropped to 130/80 mmHg, and his severe headache disappeared. One year after the cerebrovascular stroke, the telmisartan was discontinued because his blood pressure stabilized at a normal level. His plasma vascular endothelial growth factor levels were measured via specific enzyme-linked immunosorbent assay before and after the intravitreal injections of aflibercept. Immediately before the injections, the vascular endothelial growth factor level was 28 pg/ml, but it rapidly fell below the detection limit within 1 week, where it remained for over 2 months. Two days before the cerebral hemorrhage, his plasma vascular endothelial growth factor level was below the detection limit, and 2 months later after the stroke, his plasma vascular endothelial growth factor level recovered to 41 pg/ml. CONCLUSION: This case suggests that hypertension and resultant cerebral hemorrhage can occur in patients with diabetic macular edema when plasma vascular endothelial growth factor levels are systemically decreased below the detection limit for a prolonged time after local injections of anti-vascular endothelial growth factor agents into the vitreous cavity. Therefore, severely reduced plasma vascular endothelial growth factor levels could be a higher risk factor to develop generally infrequent stroke. Ophthalmologists should be aware of possible severe reduction of plasma vascular endothelial growth factor levels and resultant increase in blood pressure after intravitreal injections of an anti-vascular endothelial growth factor drug. If the plasma vascular endothelial growth factor levels could be monitored more easily and quickly during the treatment, it would help to prevent adverse events.

Safety and efficacy of unilateral and bilateral pallidotomy for primary dystonia.

OBJECTIVE: Ablation of the globus pallidus internus (pallidotomy) is an effective surgical intervention for dystonia. However, the current literature on the efficacy and safety of pallidotomy for dystonia is derived only from single-case reports and small cohort studies. METHODS: We retrospectively analyzed patients with primary dystonia who underwent pallidotomy at our institution between 2014 and 2019. Neurological conditions were evaluated using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS, range: 0-120). We evaluated the total BFMDRS score and each subitem score (nine body regions) in the patients who underwent unilateral and bilateral pallidotomy before surgery and at last available follow-up. Moreover, postoperative complications were analyzed. RESULTS: We found that 69 and 20 patients underwent unilateral and bilateral pallidotomy respectively. The mean age at dystonia onset was 40.4 ± 15.2 years. The mean clinical follow-up period was 17.2 ± 11.6 months. Unilateral pallidotomy significantly improved the total BFMDRS score from 11.2 ± 14.7 preoperatively to 5.4 ± 7.6 at last available follow-up (51.8% improvement, p < 0.001). Furthermore, there was a significant and independent improvement in all midline BFMDRS subitems, including eyes, mouth, speech/swallow, and neck, after unilateral pallidotomy. Bilateral pallidotomy significantly improved the total BFMDRS score from 14.6 ± 10.2 preoperatively to 3.8 ± 8.2 at last available follow-up (74.0% improvement, p < 0.001). However, bilateral pallidotomy induced medically refractory parkinsonism (postural instability and gait disturbance) in five patients, dysarthria in three patients, and dysphagia in one patient. INTERPRETATION: Unilateral radiofrequency pallidotomy remains a viable treatment option for patients with some forms of dystonia. Bilateral pallidotomy cannot be recommended due to unacceptably high complication rates.

[Bilateral Pallidal Deep Brain Stimulation for Dystonic Camptocormia Induced by Repetitive Abdominal Muscle Exercise:A Case Report].

Camptocormia is a rare and disabling movement disorder resulting in forward bending of the trunk. Camptocormia has many etiologies, although it is frequently observed patients with in Parkinson's disease and dystonia. Deep brain stimulation(DBS)of the globus pallidus internus(GPi)and subthalamic nucleus effectively treats camptocormia in Parkinson's disease and dystonia patients. Herein, we report a case of dystonic camptocormia induced by repetitive abdominal muscle exercise in which treatment was administered using bilateral GPi-DBS. A 54-year-old woman developed dystonic camptocormia at 53 years of age. Prior to the onset of symptoms, she regularly performed 200 abdominal muscle exercises per day. Oral medications, and botulinum toxin and lidocaine injections, were ineffective. Truncal anterior bending occurred while standing and walking. The patient underwent bilateral GPi-DBS, which instantly and dramatically improved her symptoms. The Burke-Fahn-Marsden dystonia rating scale subscore for the trunk before and after bilateral pallidotomy was 6 and 0, respectively. No perioperative adverse events were observed. Symptomatic relief persisted for 2 years. This case suggest that camptocormia can result from repeated abdominal muscle exercise, and that bilateral GPi-DBS may be a feasible and long-term efficacious procedure for dystonic camptocormia.

Safety and long-term efficacy of ventro-oral thalamotomy for focal hand dystonia: A retrospective study of 171 patients.

OBJECTIVE: To report the safety and long-term efficacy of ventro-oral thalamotomy for 171 consecutive patients with task-specific focal hand dystonia. METHODS: Between October 2003 and February 2017, 171 consecutive patients with task-specific focal hand dystonia underwent unilateral ventro-oral thalamotomy. Etiologies included writer's cramps (n = 92), musician's dystonias (n = 58), and other occupational task-related dystonias (n = 21). The task-specific focal hand dystonia scale was used to evaluate patients' neurologic conditions (range 1-5, high score indicated a better condition). The scores before surgery; at 1 week, 3 months, and 12 months postoperatively; and the last available follow-up period were determined. Postoperative complications and postoperative recurrence were also evaluated. RESULTS: The scores before surgery; at 1 week (1.72 ± 0.57, 4.33 ± 0.85 [p < 0.001]), 3 months (4.30 ± 1.06 [p < 0.001]), and 12 months (4.30 ± 1.13 [p < 0.001]); and the last available follow-up (4.39 ± 1.07 [p < 0.001]) postoperatively improved. The mean clinical follow-up period was 25.4 ± 32.1 months (range: 3-165). Permanent adverse events developed in 6 patients (3.5%). Eighteen patients developed recurrent dystonic symptoms postoperatively. Of these 18 patients, 9 underwent ventro-oral thalamotomy again, of which 7 achieved improvement. CONCLUSION: Ventro-oral thalamotomy is a feasible and reasonable treatment for patients with refractory task-specific focal hand dystonias. Prospective, randomized, and blinded studies are warranted to clarify more accurate assessment of the safety and efficacy of ventro-oral thalamotomy for task-specific focal hand dystonia. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with task-specific focal hand dystonia, ventro-oral thalamotomy improves dystonia.

Radiofrequency Lesioning Through Deep Brain Stimulation Electrodes in Patients with Generalized Dystonia.

BACKGROUND: Deep brain stimulation (DBS) is an established treatment for generalized dystonia. However, the DBS device is sometimes removed owing to hardware complications. We present 4 cases of generalized dystonia treated with radiofrequency lesioning through DBS electrodes. CASE DESCRIPTION: Four patients, 3 men and 1 woman (age range, 34-44 years), underwent DBS for generalized dystonia and subsequently developed complications, such as infection, necessitating removal of the devices. As stopping the stimulation caused recurrence of uncontrollable symptoms, radiofrequency lesioning was performed through the DBS electrodes under local anesthesia, and the DBS systems were removed under local or generalized anesthesia thereafter. The procedures performed were as follows: 2 patients had bilateral pallidotomy, 1 patient had unilateral pallidotomy, and 1 patient had pallidotomy and ipsilateral thalamotomy. As a result, in 4 patients, the dystonic symptoms did not worsen even after removal of the DBS systems during a follow-up period of 1-12 years. However, 1 patient had a small hemorrhage, and 2 patients showed recurrence of dystonia. CONCLUSIONS: Radiofrequency lesioning with DBS electrodes is feasible in cases of generalized dystonia when the DBS leads have to be removed.

Stereotactic Radiofrequency Lesioning for Movement Disorders.

During the past 2 decades, deep brain stimulation (DBS) took over the position of radiofrequency (RF) lesioning of thalamic or pallidal targets for control of movement disorders. Superiority of DBS over RF lesioning is widely accepted, and most neurosurgeons even regard RF lesioning to be old-fashioned and dangerous. Such concepts emerged from the data of old stereotactic operations with ventriculography and without computerized planning. Hardware-related complications are not negligible in long-term DBS therapy, and DBS only controls the symptoms. Living with an implanted device is also a burden for patients. With modern stereotactic techniques, RF lesioning is safe and effective. Indication of RF lesioning includes various types of tremor, focal hand dystonia, and even generalized or segmental dystonias. Neurosurgeons armed with both the procedures can choose the best treatment modality for patients.

Long-term outcome of pallidal stimulation for Meige syndrome.

OBJECTIVE Meige syndrome is characterized by blepharospasm and varied subphenotypes of craniocervical dystonia. Current literature on pallidal surgery for Meige syndrome is limited to case reports and a few small-scale studies. The authors investigated the clinical outcomes of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in patients with Meige syndrome. METHODS Sixteen patients who underwent GPi DBS at the Tokyo Women's Medical University Hospital between 2002 and 2015 were included in this study. Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) movement subscale (BFMDRS-M) scores (range 0-120) obtained at the following 3 time points were included in this analysis: before surgery, 3 months after surgery, and at the most recent follow-up evaluation. RESULTS The patients' mean age (± SD) at symptom onset was 46.7 ± 10.1 years, and the mean disease duration at the time of the authors' initial evaluation was 5.9 ± 4.1 years. In 12 patients, the initial symptom was blepharospasm, and the other 4 patients presented with cervical dystonia. The mean postoperative follow-up period was 66.6 ± 40.7 months (range 13-150 months). The mean total BFMDRS-M scores at the 3 time points were 16.3 ± 5.5, 5.5 ± 5.6 (66.3% improvement, p < 0.001), and 6.7 ± 7.3 (58.9% improvement, p < 0.001). CONCLUSIONS The results indicate long-term efficacy for GPi DBS for the majority of patients with Meige syndrome.

Pallidotomy for Writer's Cramp after Failed Thalamotomy.

BACKGROUND/AIMS: Although many reports have confirmed the effects of stereotactic thalamotomy for writer's cramp, pallidotomy for writer's cramp is yet to be investigated. METHODS: After a 22-year-old woman with writer's cramp had undergone stereotactic thalamotomy twice, symptomatic relief was only temporary. Because her dystonic symptoms spread around the proximal part of the upper limb, she underwent unilateral pallidotomy 21 months after the second thalamotomy. RESULTS: Unilateral pallidotomy improved her dystonic symptoms without any adverse effects immediately after the surgery. During a follow-up observation of 1 year, no recurrent writer's cramp was observed. CONCLUSION: For writer's cramp, when symptoms cannot be improved by thalamotomy, pallidotomy may achieve an effective outcome.

Bilateral Pallidotomy for Cervical Dystonia After Failed Selective Peripheral Denervation.

BACKGROUND: We investigated the utility of pallidotomy for cervical dystonia after failed selective peripheral denervation. CASE DESCRIPTION: A 36-year-old man presented with cervical dystonia with limited range of motion of the left shoulder, particularly in abduction. His Tsui score was 8. Owing to the ineffectiveness of botulinum toxin injection, he underwent selective peripheral denervation with an unsatisfactory outcome, with a postoperative Tsui score of 6. Simultaneous bilateral pallidotomy was performed with local anesthesia 1 year after the initial surgery. The day after the pallidotomy, all dystonic symptoms were markedly improved except for the limited range of shoulder abduction. The Tsui score recorded 1 week after the pallidotomy was 1. Transient aggressive behavior was the only postoperative complication. During clinical follow-up period of 1 year, no recurrence of the symptoms was observed. CONCLUSIONS: Pallidotomy represents a feasible and effective treatment for cervical dystonia refractory to selective peripheral denervation without hardware-related complications.

[Intrathecal baclofen therapy for hereditary spastic paraplegia].

Intrathecal baclofen therapy (ITB) is an established treatment for intractable spasticity. More than 1,100 patients have undergone ITB in Japan, and there are about 50 hereditary spastic paraplegia (HSP) The features of ITB in HSP are 1. small doses of baclofen may often be enough, 2. small changes of doses later the symptoms remarkably, 3. doses can be decreased after long term ITB.

Perimesencephalic nonaneurysmal subarachnoid hemorrhage with unilateral third cranial nerve palsy: two case reports.

Perimesencephalic nonaneurysmal subarachnoid hemorrhage (PNSAH) is a benign form of subarachnoid hemorrhage and is usually not associated with any focal deficit. We describe two rare cases of PNSAH with unilateral third cranial nerve palsy. Both patients were treated conservatively. The outcomes of our two cases were excellent. The third cranial nerve palsy resolved gradually in both patients, suggesting that the prognosis for third cranial nerve palsy concomitant with PNSAH is favorable. Unilateral third cranial nerve palsy may occur as the first clinical manifestation of PNSAH.

An autopsy case of pseudoxanthoma elasticum: histochemical characteristics.

An autopsy case of pseudoxanthoma elasticum is reported. A Japanese female patient complained of yellow papules on the neck, precordium, and axilla, beginning at 54 years of age. When the patient was 58 years old, in response to her visual disturbance a funduscopic examination was performed, revealing angioid streaks, and skin biopsy identified a characteristic pseudoxanthoma elasticum (PXE) lesion. The patient developed congestive heart failure, and following mitral valve prolapse and regurgitation flow into the left atrium, mitral valve replacement with a prosthetic valve was performed when the patient was 65 years old. Soon afterward, the patient complained of gait disturbance, and she died of congestive heart failure at 68 years of age. Autopsy specimen revealed fragmented, granular, and calcified elastic fibers in the middle to deep dermis and in the thickened subendocardium, and small to medium-sized muscular arteries revealed fragmented, laminated, and calcified elastic lamina; vascular changes were seen in the heart, lung, kidney, gastrointestinal tract, and iliac artery. Disrupted elastic fibers were visualized using the Weigert resorcin fuchsin method and were stained positive by antielastin and antifibronectin antibodies. Calcification was confirmed by von Kossa staining. Affected areas were PAS-positive after diastase digestion, indicating the presence of glycoprotein. Affected areas were colloidal iron-positive, indicating the presence of proteoglycan matrix.

A study of abnormal cervical cytology in pregnant women.

During the 4-year routing study of smears in 2,919 pregnant women, 33 cases of abnormalities of the uterine cervix were detected (1.13%). The patients were followed with uterine cervical cytology and colposcopy, and in case of need, sometimes punch biopsies were performed. As a result of the cytologies, 33 cases with abnormalities were detected. There were 26 cases classified as class IIIa and 7 cases were class IIIb. All cases underwent colposcopy. For the 17 cases that showed lesions by colposcopy, punch biopsies were performed. The results of histologic examination were wide: 5 chronic cervicitis, 1 condyloma, 1 mild dysplasia, 3 moderate dysplasia, 3 severe dysplasia, 3 carcinoma in situ, and 1 microinvasive carcinoma. Only two cases were treated during pregnancy, condyloma underwent Laser vaporization and microinvasive carcinoma underwent Loop electrosurgical excision procedure (LEEP) conization. Other cases were conservative treatment during pregnancy. Excluding one case for persistence smear class IIIa of histology condyloma, all the other cases with regression of dysplasia and carcinoma in situ with treatment after delivery. We conclude that lesions up to carcinoma in situ do not require intervention during pregnancy but microinvasive carcinoma is suspected, diagnostic LEEP conization is necessary, even during pregnancy.

A study of abnormal cervical cytology in pregnant women.

During the 4 year routine study of smears in 2,919 pregnant women, 33 cases of abnormals of the uterine cervix were detected (1.13%). The patients were followed with uterine cervical cytology and colposcopy and in case of need, sometimes punch biopsies were performed. The results of the cytologies, 33 cases with abnormalities were detected. There were 26 cases classified as class IIIa, 7 cases were class IIIb. All the cases underwent colposcopy. For the 17 cases that showed lesions by colposcopy, and punch biopsies were performed. The results of histologic examination were wide variety, five chronic cervicitis, one condyloma, one mild dysplasia, three moderate dysplasia, three severe dysplasia, three carcinoma in situ, and one microinvasive carcinoma. Only two cases were treated during pregnancy; one with condyloma underwent Laser vaporization and another with microinvasive carcinoma underwent LEEP conization. Other cases were given conservative treatment during pregnancy. Excluding one case for persistence smear class IIIa of histology condyloma, all the cases showed regression of dysplasia and carcinoma in situ with treatment after delivery. We conclude that lesions up to carcinoma in situ do not require intervention during pregnancy but microinvasive carcinoma is suspected, diagnostic LEEP conization is necessary, even during pregnancy.